UCL70805F in Patients With CD70-positive Advanced Renal Clear Cell Carcinoma

An Exploratory Clinical Study to Evaluate the Safety and Preliminary Efficacy of UCL70805F in the Treatment of Patients With CD70-positive Advanced Renal Clear Cell Carcinoma

This is a single-arm, open-label, exploratory clinical study to evaluate the safety and preliminary efficacy of UCL70805F in patients with CD70-positive advanced renal clear cell carcinoma.

This study will include two parts, dose escalation phase (modified "3+3" design) followed by a dose expansion phase.

All eligible participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, followed by a single intravenous infusion of UCL70805F. The recommended phase 2 dose (RP2D) will be determined during the dose escalation phase. In the dose expansion phase, one or two dose levels may be selected to further characterize the safety profile and evaluate the efficacy of UCL70805F.

Inclusion Criteria:

• Age from 18 to 75 years old (inclusive), gender is not limited.
• Histopathologically confirmed advanced clear cell renal cell carcinoma (ccRCC) that has failed prior standard therapy, or is intolerant to standard therapy, or for which no effective treatment is available.
• At least one measurable target lesion as defined by RECIST v1.1.
• Fresh solid tumor samples or formalin fixed paraffin embedded tumor archival samples are necessary.
• CD70 should be positive confirmed by Immunohistochemistry (IHC) in tumor tissue samples (H-Score > 100 for CD70 membrane expression).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy ≥ 3 months.
• The organ function must meet the protocol requirements.
• Female participants of childbearing potential must have a negative pregnancy test. Female participants of childbearing potential or male participants have partners of childbearing potential must agree to use effective contraception throughout the screening period until 1 year after the last cell infusion.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Pregnant or lactating women.
• Hepatitis C virus (HCV) antibody positive with quantitative PCR for peripheral blood HCV RNA above the lower limit of detection; human immunodeficiency virus (HIV) antibody positive; or active syphilis infection.
• HBV surface antigen (HBsAg) positive and/or HBV core antibody (HBcAb) positive, with HBV-DNA ≥ 500 IU/mL.
• Unresolved > Grade 1 non-hematologic toxicity per CTCAE 5.0 associated with any prior treatments (surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.), except for alopecia, peripheral sensory neuropathy.
• History of allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation, etc.), except for transplants not requiring immunosuppressive therapy (e.g., corneal transplantation, hair transplantation).
• Receipt of other CD70-targeted CAR-T cell therapy.
• Major surgery procedure without full recovery within 4 weeks prior to signing the informed consent, or a history of severe trauma that have not recovered, or plan to receive major surgery procedure within 12 weeks after cell infusion.
• Known central nervous system metastasis lesions, except for the following participants: a. asymptomatic brain metastases; b. clinically stable status (i.e., no radiological progression within 4 weeks prior to cell apheresis, and any neurological symptoms have resolved to baseline level), and have not required corticosteroids or other therapy for brain metastases for ≥ 4 weeks.
• Presence of clinically significant systemic disease (e.g., severe active infection or significant dysfunctions of the heart, lungs, liver, nervous system, or other organs), at the discretion of the Investigator, impairs the participant's ability to tolerate the treatment specified in this trial protocol or significantly increases the risk of complications.
• History of severe systemic hypersensitivity to the drugs/components used in this trial [e.g., fludarabine, cyclophosphamide, dimethyl sulfoxide (DMSO), low molecular weight dextran, human serum albumin (HSA)].
• Receipt of live attenuated vaccine within 4 weeks prior to signing informed consent.
• Participation in another clinical trial within 4 weeks prior to signing informed consent.
• History of another malignancy within the past 5 years, except for adequately treated basal cell carcinoma of the skin or carcinoma in situ (e.g., breast, stomach, colon, cervix, etc.).
• History of neuropsychiatric disorders diagnosed per ICD-11 criteria, or any neuropsychiatric disorder requiring exclusion as determined by the investigator, including but not limited to epilepsy, schizophrenia, dementia, or drugs/alcohol addiction.
• Any other condition that, in the investigator's opinion, makes the patient unsuitable for participating in this trial.